As the list of patients needing transplants grows, while the pool of available organs stagnates the search for new sources of donor organs becomes increasingly relevant. Efforts to enhance the yield from potential human donors have included campaigns to increase public and physician awareness of organ donation, greater emphasis on living donors, and relaxation of acceptance criteria for cadaver donors. Despite these efforts, an allogeneic solution seems unlikely. As a result, xenotransplantation, the transplantation of tissues and organs between species, is undergoing serious consideration.

In xenotransplantation, species combinations have typically been designated as either concordant or discordant, depending on whether or not hyperacute rejection (HAR) results. But over the past two decades, study of the pathobiology of xenograft rejection has demonstrated this classification system to be greatly oversimplified; it is not necessarily based on the pathogenesis of the rejection process observed in different species combinations. This review avoids broad categorization, and instead discusses xenografting in terms of the phylogenetic disparity of specific species pairs and the underlying mechanisms of xenograft loss. In addition, the processes which lead to graft loss even if HAR is prevented (i.e., beyond HAR) are discussed.

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